The Anesthetic Effect of Ultrasound-Guided Serratus Anterior Plane Block in Arthroscopic Shoulder Surgery and Its Effect on Postoperative Analgesia.
To investigate the anesthetic effect of anterior serratus muscle plane block under ultrasound guidance in arthroscopic shoulder surgery and its effect on postoperative analgesia. A total of 94 patients who received arthroscopic shoulder surgery in our hospital were selected as the research subjects, and they were divided into a control group and a study group according to the random number table method. The control group underwent brachial plexus block under ultrasound guidance, and the study group underwent anterior serratus plane block under ultrasound guidance. The visual analogue score (VAS) of pain at each time point, intraoperative anesthetic dosage, the use of postoperative analgesic, pain mediators and oxidative stress factors before and after surgery, and the occurrence of adverse reactions were compared between the two groups after surgery. At 6, 12, 48, and 72 h after surgery, there was no obvious difference in the VAS score between the two groups (P > 0.05); 24 h after surgery, the VAS score of the study group was significantly lower than that of the control group (P < 0.05). The intraoperative dosage of propofol and remifentanil in the study group was significantly lower than that in the control group (P < 0.05). The number of effective compressions of analgesic pump and the total amount of sufentanil in the study group were significantly lower than those in the control group within 48 hours after operation, and the time of first compressions of analgesic pump was significantly longer than that in the control group (P < 0.05). Before surgery, there were no significant differences in CGRP, NPY, and MDA levels and SOD enzyme activity between the two groups (P > 0.05). After surgery, the levels of pain mediators CGRP and NPY in the study group were lower than those in the control group (P < 0.05). The level of MDA was lower than that of the control group, and SOD enzyme activity was higher than that of the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Ultrasound-guided anterior serratus plane block for arthroscopic shoulder surgery has a good anesthesia effect and long action time. It can significantly reduce the dosage of opioids, enhance the postoperative analgesic effect, effectively inhibit postoperative pain and oxidative stress reaction, and has good safety.


The effect of repeated intramuscular alfentanil injections on experimental pain and abuse liability indices in healthy males.
Opioid-induced hyperalgesia (OIH), increased sensitivity to noxious stimuli after repeated opioid exposures, has been demonstrated in preclinical studies. However, there is no accepted, prospective model of OIH after repeated opioid exposures currently available in humans. This study assessed a potential prospective OIH model. Double-blind intramuscular injections of a short-acting opioid (alfentanil 15 mcg/kg; N=8) were compared to active placebo (diphenhydramine 25 mg; N=3) on cold and pressure pain testing and standard abuse liability measures in eight 10-hour sessions (1 injection/session) over 4 to 5 weeks in healthy, pain-free males. Decreases from session baseline pain threshold (PThr) and tolerance (PTol) were calculated to represent hyperalgesia, and were assessed both within and across sessions. Mean decreases in cold PTol were seen in the alfentanil group at 180 minutes (-3.8 s, ±26.5) and 480 minutes (-1.63 s, ±31.5) after drug administration. There was a trend for differences between conditions on cold PThr hyperalgesia but not for pressure PThr. Alfentanil participants had greater mean ratings on Liking and High visual analog scales at peak effects (30 min), but these scores did not change across sessions. Repeated alfentanil exposures over 4 to 5 weeks resulted in within session decreases in cold pain tolerance from baseline but these differences were not substantially different from diphenhydramine controls. The results did not support the phenomenon of OIH in this model, although definitive conclusions regarding the existence of OIH in humans likely requires a larger sample size or an alternative model.


Optimal timing for performing hysterectomy according to different phase of menstrual cycle: Which is best?
The aim of this study was to determine whether the different phases of the menstrual cycle could affect operative bleeding in women undergoing laparoscopic hysterectomy. This was a retrospective comparative study. Based on the adjusted day of menstrual cycle, 212 women who underwent laparoscopic hysterectomy were classified into three groups: the follicular phase (n = 51), luteal phase group (n = 125), and menstruation group (n = 36). The primary outcome measure was the operative bleeding. There was no difference in the baseline characteristics of the patients belonging to the three groups. For the groups, there were no significant differences in operative bleeding (p = .469) and change in haemoglobin (p = .330), including operative time, length of hospital stay and complications. The menstrual cycle did not affect the operative bleeding and other parameters. Therefore, no phase of the menstrual cycle could be considered as an optimal timing for performing laparoscopic hysterectomy with minimal operative bleeding. Impact statement What is already known on this subject: the menstrual cycle results in periodic changes in haemostasis and blood flow in the reproductive organs. What the results of this study add: the menstrual cycle did not affect the operative bleeding and other operative parameters during laparoscopic hysterectomy. What the implications are of these findings for clinical practice and/or further research: no phase of the menstrual cycle could be considered as an optimal timing for performing laparoscopic hysterectomy with minimal operative bleeding.


Intramolecular ring-opening from a CO2-derived nucleophile as the origin of selectivity for 5-substituted oxazolidinone from the (salen)Cr-catalyzed [aziridine + CO2] coupling.
The (salen)Cr-catalyzed [aziridine + CO2] coupling to form oxazolidinone was found to exhibit excellent selectivity for the 5-substituted oxazolidinone product in the absence of any cocatalyst. Quantum mechanical calculations suggest that the preferential opening of the substituted C-N bond of the aziridine over the unsubstituted C-N bond is a key factor for this selectivity, a result that is supported by experiment with several phenyl-substituted aziridines. In the presence of external nucleophile such as dimethyl aminopyridine (DMAP), the reaction changes pathway and the ring-opening process is regulated by the steric demand of the nucleophile.


Endurance training effects on plasma hormonal responsiveness and sex hormone excretion.
A prospective study of the hormonal effects of a moderate exercise training program (4-wk control, 8-wk training) was conducted in seven young women. Sixty-minutes continuous bicycle ergometer tests of fixed relative intensity were performed at the beginning, middle, and end of the training period. The capacity of these acute bouts of exercise to affect circulating levels of stress markers, reproductive hormones, and hormones with possible antireproductive potential was measured. In addition, the urinary excretion of reproductive hormones was monitored continuously via serial overnight urine collections. Within testing sessions, plasma concentrations of all stress markers and antireproductive hormones rose significantly. Across testing sessions, only beta-endorphin + beta-lipotropin and cortisol exhibited an increment in peak responses as training progressed. Plasma reproductive hormone levels showed insignificant acute changes, and cyclic menstruation and preovulatory gonadotropin surges continued in all subjects. However, ovarian function was disturbed in four subjects as evidenced by a decreased excretion of estriol, free progesterone, or both. Transient infertility is a known clinical accompaniment of hormonal changes of comparable subtlety.


Resonant tunneling of interacting electrons in a one-dimensional wire.
We consider the conductance of a one-dimensional wire interrupted by a double-barrier structure allowing for a resonant level. Using the electron-electron interaction strength as a small parameter, we are able to build a nonperturbative analytical theory of the conductance valid in a broad region of temperatures and for a variety of the barrier parameters. We find that the conductance may have a nonmonotonic crossover dependence on temperature, specific for a resonant tunneling in an interacting electron system.


Puff, puff, drink: The association between blunt and alcohol use among African American adolescents and young adults.
Although African Americans report lower levels of alcohol use relative to their White counterparts, they experience higher rates of alcohol-related problems (e.g., alcohol dependence). One understudied connection between alcohol use and dependence is the dual use of illicit drugs, especially marijuana use. It is speculated that blunt use in combination with alcohol will have more adverse alcohol-related consequences among African Americans than alcohol use alone or alcohol and nonblunt marijuana use. The current study uses pooled data from the 2011-2014 National Survey on Drug Use and Health to examine the odds of alcohol dependence based on alcohol and marijuana typology in comparison to alcohol only users. Among 11,124 African American adolescents (12-17) and young adults (18-25) who consumed alcohol in the past year, 57.5%, 36.8%, and 5.7% reported alcohol use alone and in combination with blunt use and nonblunt marijuana use, respectively. Relative to alcohol users only, youth who used alcohol and blunts had increased odds of having alcohol dependence. This association was not found among youth who reported alcohol and nonblunt marijuana use. The increased rates of alcohol dependence highlight the public health concern of dual alcohol and a specific type of marijuana use (i.e., blunts) among African American youth. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Selective recognition of configurational substates of zinc cyclam by carboxylates: implications for the design and mechanism of action of anti-HIV agents.
The interaction of metal cyclams with carboxylate groups is thought to play an important role in their binding to the CXCR4 chemokine receptor and in their anti-HIV activity. Here we report the synthesis of acetate, phthalate, perchlorate and chloride complexes of Zn(II) cyclam (1,4,8,11-tetraazacyclotetradecane). The X-ray crystal structures of [Zn(cyclam)(phthalate)](n)(CH(3)OH)(2n) and [Zn(cyclam)(H(2)O)(2)](OAc)(2) contain octahedral Zn(II) centres. Phthalate acts as a bridging ligand in the former complex, binding through monodentate carboxylate groups, and giving rise to infinite chains in the lattice together with extensive hydrogen bonding between carboxylate donor oxygen atoms and amine and methanol acceptor atoms. The uncoordinated acetate groups and the aqua ligand in the acetate complex are also involved in a rich network of hydrogen bonds and this may account for the unusually long Zn[bond]O distance (2.27 A). In both crystalline complexes, the macrocycle adopts the trans-III (S,S,R,R) configuration. 1D (1)H NMR spectra of all four complexes have been fully assigned by a combination of 2D [(1)H, (1)H] COSY and TOCSY, and [(1)H, (13)C] and [(1 )H, (15)N] HSQC NMR data. In aqueous solution, the stable trans-III configuration found in the solid-state equilibrates slowly (hours at 298 K) with trans-I (R,S,R,S) and cis-V (R,R,R,R) configurations. The trans-III configuration is predominant in aqueous solution for both the chloride and perchlorate complexes, but for the acetate and phthalate complexes, the cis-V configuration dominates. Carboxylate groups appear to stabilize the cis-V configuration in solution through Zn(II) coordination and hydrogen bonding. Titration of the chloride Zn(II)-cyclam complex with acetate confirmed that carboxylates strongly induce formation of the cis-V configuration. This implies that carboxylates can exert a strong influence over configurational selectivity. Cyclam NH hydrogen bonding is prevalent both in the solid state and in solution, and is relevant to the anti-HIV activity of Zn(II) and other metal cyclam complexes and to their ability to recognize the CXCR4 transmembrane co-receptor.


The noncoding genome: implications for ruminant reproductive biology.
Advances in the analyses of human and other higher eukaryotic genomes have disclosed a large fraction of the genetic material (ca 98%) which does not code for proteins. Major portion of this non-coding genome is in fact transcribed into an enormous repertoire of functional non coding RNA molecules (ncRNAs) rather than encoding any proteins. Recent fascinating and fast progress in bioinformatic, high-throughput sequencing and other biochemical approaches have fuelled rapid growth in our appreciation of the tremendous number, diversity and biological importance of these ncRNAs in the hidden layer of gene regulation both at transcriptional and post-transcriptional level. Broadly ncRNAs fall into three size classes namely, 20 nucleotides for the large family of microRNAs (miRNAs), to 25-200 nucleotides for other different families of small RNAs and finally to over thousands of nucleotides for macro ncRNAs involved in eukaryotic gene regulation. Among the ncRNAs that have revolutionized our understanding of eukaryotic gene expression, microRNAs (miRNAs) have recently been emphasized extensively with enormous potential for playing a pivotal role in disease, fertility and development. They are found to be potentially involved in various aspects of physiological regulation of reproductive tissues (testis, ovary, endometrium and oviduct), cells (sperm and oocytes) and embryonic development in addition to other body systems. Here, we review the recent work on miRNAs in details and some other small ncRNAs briefly in animal models focusing on their diverse roles in the physiology of reproductive cells and tissues together with their implications for ruminant reproductive biology.


[Biological diagnosis of Schistosoma infestation].
For general practitioners the most important step towards the clinical and laboratory diagnosis of infestation with Schistosoma spp. is to think of it. Although schistosomiasis is the world's most frequent parasitosis after malaria, it is found in France only as imported cases (immigrants, tourists, etc.) with clinical signs that are not always very suggestive at the stage of invasion. The laboratory examinations requested can then make the diagnosis, irrespective of the time elapsed since infestation. In the early invasion stage, only the indirect serological methods (ELISA, IFI, precipitation techniques) are appropriate. The direct methods are not always informative since the parasites are still immature and do not lay eggs. But when the disease is established the diagnosis rests essentially on direct examination of urine and faeces which discloses schistosoma eggs the morphology of which varies from one species to the other.


A novel congenital diaphragmatic hernia prediction model for Chinese subjects: A multicenter cohort investigation.
Brindle et al. (2014) and the Congenital Diaphragmatic Hernia Study Group constructed a simplified clinical prediction rule (Brindle score) to stratify infants with congenital diaphragmatic hernia based on disease severity. We aimed to develop a predictive model applicable to Chinese patients with congenital diaphragmatic hernia and externally validate whether the Brindle score is applicable to the Chinese population. Multiple imputations supplemented the missing data. A least absolute shrinkage and selection operator regression was used to screen the factors influencing adverse outcomes. Internal validation was performed by bootstrap resampling. The C-index, area under the receiver operating characteristic curve, and the Hosmer-Lemeshow test evaluated the predictive power. A nomogram named "CCDH score" (Chinese Congenital Diaphragmatic Hernia score), including pulmonary hypertension, low 5-min Apgar score (<7), chromosomal anomaly, major cardiac anomalies (MCAs), observed-to-expected lung-to-head ratio, and the percentage of liver herniation, was constructed. The CCDH score revealed good calibration and discriminative abilities, with a C-index of 0.941. In the training and external validation cohorts, the area under the receiver operating characteristic curve of the Brindle score were 0.820 and 0.881, respectively. The Brindle score has fair predictive power in the Chinese population, but the newly established CCDH score seems more suitable for Chinese patients with congenital diaphragmatic hernia. The CCDH score is the first predictive model constructed based on the characteristics of the Chinese population and can accurately predict the survival outcomes of patients with congenital diaphragmatic hernia.


[Effect of Tripterygium Glycosides Tablets on immune-induced liver and kidney function in patients with rheumatoid arthritis based on data mining].
This paper aims to investigate the effect of oral administration of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on immune inflammatory index in patients with rheumatoid arthritis,in order to explore the compatibility mode of traditional Chinese medicine in the treatment of rheumatoid arthritis. Medical records of hospitalized patients with rheumatology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2012 to December 2017 were collected. The combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine was adopted for the experimental group,while the simply administration of Tripterygium Glycosides Tablets were adopted for the control group. SPSS 21. 0 was used to analyze the changes of general conditions and immune inflammatory metabolic indexes in the two groups of RA patients. The association rules were analyzed by SPSS Clementine 14. 2 software Apriori module,and the random walk model was evaluated by ORACLE 10 g tool. The results showed that a total of 1 220 patients with rheumatoid arthritis met the requirements of this study,including 322 in the experimental group and 898 in the control group. Before treatment,there was no significant difference in age and duration between the two groups. The difference value of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR in the two groups of RA patients decreased before and after treatment,and the experimental group was superior to the control group in reduction of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR.The control group was superior to the experimental group in reduction of Ig M( P<0. 01 or P<0. 05). Compared with before treatment,ALT,AST,ALP,GGT,CREA,BUN,b-MG,MA,TRU and Ig U all increased,with statistically significant differences( P<0. 01).The UA of the two groups of RA patients decreased after treatment,with statistically significant differences( P<0. 01). The experimental group was superior to the control group in reduction of UA,with statistically significant differences( P < 0. 05 or P < 0. 01). The herbs adopted in the prescriptions of 1 220 patients were mainly classified into four categories,namely spleen-sweating herbs,blood-activating and stasis-relieving herbs,phlegm and phlegm-relieving herbs,and heat-clearing and antidote herbs. The results of association rule analysis indicated a significant correlation between the single-flavored Tripterygium Glycosides Tablets,oral Chinese medicine and immune inflammation,and improvement of liver and kidney function indexes. The results of the random walk model analysis indicated that the experimental group's Ig M and hs-CRP were superior to those of the control group in terms of random fluctuation maximum,walking positive growth rate,comprehensive evaluation index increasing rate,comprehensive improvement rate,comprehensive evaluation index recording times,and expected improvement value. The results of this study showed that the single administration of Tripterygium Glycosides Tablets can effectively improve the immune inflammatory metabolic index of patients with rheumatoid arthritis,and the combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine could alleviate the immune inflammatory index of RA patients and reduce liver and kidney dysfunction compared with simple oral administration. The comprehensive evaluation Ig M and hs-CRP in the group of combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine were better than those in the group of the Tripterygium Glycosides Tablets. There was a long-term correlation between the comprehensive evaluation index and the intervention measures of the two groups of patients.


Anti-leukaemic activity of the TYK2 selective inhibitor NDI-031301 in T-cell acute lymphoblastic leukaemia.
Activation of tyrosine kinase 2 (TYK2) contributes to the aberrant survival of T-cell acute lymphoblastic leukaemia (T-ALL) cells. Here we demonstrate the anti-leukaemic activity of a novel TYK2 inhibitor, NDI-031301. NDI-031301 is a potent and selective inhibitor of TYK2 that induced robust growth inhibition of human T-ALL cell lines. NDI-031301 treatment of human T-ALL cell lines resulted in induction of apoptosis that was not observed with the JAK inhibitors tofacitinib and baricitinib. Further investigation revealed that NDI-031301 treatment uniquely leads to activation of three mitogen-activated protein kinases (MAPKs), resulting in phosphorylation of ERK, SAPK/JNK and p38 MAPK coincident with PARP cleavage. Activation of p38 MAPK occurred within 1 h of NDI-031301 treatment and was responsible for NDI-031301-induced T-ALL cell death, as pharmacological inhibition of p38 MAPK partially rescued apoptosis induced by TYK2 inhibitor. Finally, daily oral administration of NDI-031301 at 100 mg/kg bid to immunodeficient mice engrafted with KOPT-K1 T-ALL cells was well tolerated, and led to decreased tumour burden and a significant survival benefit. These results support selective inhibition of TYK2 as a promising potential therapeutic strategy for T-ALL.


Arm x-ray assessment of percent body fat in men and women.
The present experiment determined the validity of arm radiography for quantifying total body fat in young and older men and women. One hundred subjects were measured for 1) body density by underwater weighing with correction for residual air volume to estimate percent body fat and 2) horizontal right upper arm x-ray at KV 76, exposure time 1/30th s, 300 MA, and focal length 72 inches. Total radiation was 10 millirems (mR). The width of fat on the x-ray was measured at three cross-sectional sites (FAT,x-ray). Errors of measurement and measurement for reliability were assessed from duplicate x-rays and repeated measures on the same x-rays (r = 0.92-0.99). The equation to convert FAT,x-ray to individual estimates of percent fat is %Fat = FAT,x-ray/3F X k constant, where 3F = 3 square root wt,kg/ht,dm, and the k constant is a previously determined mean value. The correlation between Fat,x-ray and percent fat (density) was r = 0.89 (N = 100, Se = +/- 2.54); for 25 young men (ages 18-30), r = 0.90 (Se = +/- 1.84); for 25 older men (ages 30-40), r = 0.89 (Se = +/- 2.20); for young (N = 25) and older (N = 25) women, r = 0.85 (Se = +/- 2.08) and 0.87 (Se = +/- 2.61), respectively. These results demonstrate that the new, arm radiogrammetric method is a reliable and valid technique for assessment of body composition in men and women ages 18-40 yr.(ABSTRACT TRUNCATED AT 250 WORDS)


[Adaptation of a diazoreaction method for determining total and conjugated bilirubins on a parallel analyser].
A diazoreaction method of estimation of bilirubin has been adapted on a FP9 parallel analyzer. Biotrol's kit could be used only after modifications of the protocol. The critical study of this adaptation included trials of within run precision (CV 1.93 to 4.42%), total precision (CV 2.59 to 6.66%) as also evaluation of analytical range: the limit of linearity is 340 mumol/l. The evaluation of inaccuracy performed with patient specimens leads to establishment of follow-up norms and interpretation norms of allometry line. Our whole results are in conformity with the performance standards of the protocol for the validation of methods published by the Société Française de Biologie Clinique. Finally the described method is quick acting, reliable and very inexpensive.


Redox regulation of the yeast voltage-gated Ca2+ channel homolog Cch1p by glutathionylation of specific cysteine residues.
Cch1p, the yeast homolog of the pore-forming subunit α1 of the mammalian voltage-gated Ca2+ channel (VGCC), is located on the plasma membrane and mediates the redox-dependent influx of Ca2+ Cch1p is known to undergo both rapid activation (after oxidative stress and or a change to high pH) and slow activation (after ER stress and mating pheromone activation), but the mechanism of activation is not known. We demonstrate here that both the fast activation (exposure to pH 8-8.5 or treatment with H2O2) and the slow activation (treatment with tunicamycin or α-factor) are mediated through a common redox-dependent mechanism. Furthermore, through mutational analysis of all 18 exposed cysteine residues in the Cch1p protein, we show that the four mutants C587A, C606A, C636A and C642A, which are clustered together in a common cytoplasmic loop region, were functionally defective for both fast and slow activations, and also showed reduced glutathionylation. These four cysteine residues are also conserved across phyla, suggesting a conserved mechanism of activation. Investigations into the enzymes involved in the activation reveal that the yeast glutathione S-transferase Gtt1p is involved in the glutathionylation of Cch1p, while the thioredoxin Trx2p plays a role in the Cch1p deglutathionylation.


A yellow-stained human femur from Tell esh-Shuqafiya, Egypt: evidence of ancient trauma.
Excavation at Tell esh-Shuqafiya, Egypt, during the 1982 season exposed several Ptolemaic Period burials. One of these, a young adult male, showed a bright yellow stain on the right femur. Analysis of the stain demonstrated it to be hematoidin, a degradation compound derived from hemoglobin associated with old hemorrhage. The specific location of the stain on the skeleton suggests death a few weeks after a severe injury to the thigh.


Intranasal oxycodone self-administration in non-dependent opioid abusers.
Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n = 8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double-blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: (1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and (2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., "like") during sample sessions (p < .05). These reports were positively correlated with self-administration behavior (e.g., "like," r = .65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be used to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment.


Is an increased vagal tone involved in the pathogenesis of gastroduodenal ulcers?
The purpose of this review is to examine the role of vagal influence on the regulation of gastric acid secretion in humans, and to answer the question as to whether there is any indication of increased vagal tonus being involved in the pathogenesis of peptic ulcers. Apart from the central importance of vagal influence on gastric acid secretion, there is no direct evidence for the existence of general vagal hyperactivity in peptic ulcer patients. Increased vagal activity can only be indirectly demonstrated for a subgroup of duodenal ulcer patients. The involvement of psychodynamic factors as a background phenomenon is emphasized.


Cooperative Activation of Cobalt-Salen Complexes for Epoxide Hydration Promoted on Flexible Porous Organic Frameworks.
Developing solid catalysts with multiple active sites working cooperatively is desirable for efficient chemical transformations. However, most solid catalysts are rigid and impede the cooperation between their spatially isolated active sites. Two flexible porous organic frameworks (POFs) with integrated Co(salen) as active sites have been successfully synthesized for mimicking the cooperative modes of enzymes. The POFs exhibit second-order rate dependence on Co(salen) concentration in the network and afford much higher TOF (3300 versus 2670 h-1 ) than the homogeneous counterpart in the hydration of propylene epoxide. POFs with a flexible network thus not only facilitate but also enhance the cooperation of nearby Co(salen). Moreover, POFs could catalyze oversized substrates, have a wide substrate scope, and exhibit high stability.


Determination of iohexol and iothalamate in serum and urine by capillary electrophoresis.
Estimation of glomerular filtration rate (eGFR) is essential to assess kidney function. Iodine-containing contrast agents detection by HPLC has been proposed as a safe alternative for inulin or radioactive compounds. However, HPLC is a time-consuming and labor-intensive method. The aim of this study was to develop an assay for iohexol and iothalamate using capillary electrophoresis. Iohexol and iothalamate were directly analyzed by CE in serum and urine, using photometric detection (246 nm). Serum peak height was proportional to iohexol and iothalamate concentrations. Detection limits for iohexol and iothalamate were 10 and 5 mg/L. Limits of quantification were 13.0 and 15.0 mg/L. Within-run CVs were 4.9 and 6.5%; between-run CVs 3.1-9.9% and 3.8-13.7%. A good correlation was observed between CE and HPLC: y = 1.1703x + 5.017 (iohexol) and y = 0.7807x + 11.01 (iothalamate; (y = concentration obtained by CE [mg/L], x = concentration obtained by HPLC [mg/L]). In addition, CE allowed to determine urinary iohexol concentration. Although the detection limit for CE was higher than for HPLC, CE can still be used for eGFR determination. Advantages of this high-throughput method are the absence of sample pretreatment and a minimal sample volume requirement.


A graphene oxide/gold nanoparticle-based amplification method for SERS immunoassay of cardiac troponin I.
Cardiac troponin I (cTnI) was considered as the "gold standard" for acute myocardial infarction (AMI) diagnosis owing to its superior cardiac specificity for cardiac damage and showing little or no changes in patients with a skeletal muscle disease or trauma. Herein, a new signal amplification surface-enhanced Raman scattering (SERS) platform was developed for recognition and detection of cTnI by using gold nanoparticles (AuNPs), graphene oxide (GO) and magnetic beads (MB). Here, antibody/Raman reporter labeled AuNP-functionalized GO were employed as both SERS nanotags and signal amplification carriers. Monoclonal antibody modified MB were applied as the capture probe and separation agents. In the presence of cTnI, sandwich type immunocomplexes, "capture probe/target/SERS nanotags", were formed through antibody-antigen-antibody interactions. Due to the strong SERS enhancement ability of the designed GO/AuNP complexes and a high binding chance between cTnI and the GO/AuNP complexes, the proposed SERS-based immunoassay could selectively detect cTnI with a high sensitivity (detection limit of 5 pg mL-1) and a good linearity was obtained in a range of 0.01-1000 ng mL-1. In addition, this method was also successfully applied for detecting cTnI in serum substitute media with a similar linear range. Furthermore, this strategy can be constructed with different kinds of antibodies and Raman reporters, and thus can be easily used for simultaneous detection of multiple biomarkers. Therefore, this proposed SERS-based signal amplification technique shows strong potential for the clinical diagnosis of AMI disease.


Psychiatric Patients' Perceived Health Control and Reactance: Implications for Medication Adherence.
Adherence to prescribed treatment is a major challenge in psychiatry, with non-adherence rates estimated to be as high as 50%. Two factors that have been suggested to influence medication adherence in psychiatric patients are perceived health control and psychological reactance. Perceived health control refers to the belief that one can control their own health outcomes, while psychological reactance refers to the negative response that occurs when individuals perceive their freedom or autonomy to be threatened. The aim of this review is to explore the possible relevance and interaction of perceived health control and psychological reactance in the adherence of psychiatric patients to their treatment. Several studies have suggested that higher levels of perceived health control are associated with better medication adherence, while higher levels of psychological reactance are associated with poorer adherence. Moreover, it has been suggested that patients with high levels of perceived health control may be more likely to experience psychological reactance if they feel that their autonomy is threatened by the treatment regimen. Taken together, these findings suggest that perceived health control and psychological reactance may interact to influence medication adherence in psychiatric patients. Future research could explore ways to enhance patients' perceived health control while minimizing psychological reactance in order to improve treatment adherence in this population.


[A cohort study on the relationship between body mass index and blood pressure, blood lipid, blood glucose, left ventricular structure and function in adolescents during transition period].
To investigate the relationship between body mass index(BMI) and blood pressure, blood lipid level, blood glucose, left ventricular structure and function in adolescents during transition period. A vertical sectional survey on 193 pupils aged 7-11 years in primary school in 1996 was performed. 9 years later, the same research subjects aged 16-20 years were studied again in 2005. The subjects were divided into obesity,overweight and normal weight groups according to their BMI in 1996. Height, body weight, blood pressure, total cholesterol, triglyceride and blood glucose were collected and analyzed, and left ventricular structure and function were examined by echocardiography. Body mass index (24.71 kg/m(2)+/-4.57 kg/m(2), 20.54 kg/m(2)+/-2.84 kg/m(2) ), systolic blood pressure (117.22 mm Hg+/-17.44 mm Hg vs. 102.20 mm Hg+/-11.68 mm Hg), thickness of inter-ventricular septum and posterior wall (0.87 cm+/-0.12 cm vs. 0.77 cm+/-0.12 cm, and 0.91 cm+/-0.13 cm vs. 0.79 cm+/-0.31 cm), left ventricular mass and mass index (167.84 g+/-16.29 g vs. 128.95 g+/-63.00 g, and 88.12 g/m(2) +/-17.19 g/m(2) vs. 79.35 g/m(2)+/-39.01 g/m(2)) were found significantly higher in obesity group than in normal weight group 9 years later (P<0.05, P< 0.01 or P< 0.001). End diastolic volume and cardiac output were increased(P <0.05) and ejection fraction and fractional shortening decreased( P< 0.05). There were no differences found in cardiac diastolic function between the studied groups. The results suggested that simple obesity in childhood was an important cardiovascular risk factor when they grew into adolescents and adults. ;


Effects of an oscillating magnetic field on homogeneous ferrofluid turbulence.
This paper presents the results from direct numerical simulations of homogeneous ferrofluid turbulence with a spatially uniform, applied oscillating magnetic field. Due to the strong coupling that exists between the magnetic field and the ferrofluid, we find that the oscillating field can affect the characteristics of the turbulent flow. The magnetic field does work on the turbulent flow and typically leads to an increased rate of energy loss via two dissipation modes specific to ferrofluids. However, under certain conditions this magnetic work results in injection, or a forcing, of turbulent kinetic energy into the flow. For the cases considered here, there is no mean shear and the mean components of velocity, vorticity, and particle spin rate are all zero. Thus, the effects shown are entirely due to the interactions between the turbulent fluctuations of the ferrofluid and the magnetic field. In addition to the effects of the oscillation frequency, we also investigate the effects of the choice of magnetization equation. The calculations focus on the approximate centerline conditions of the relatively low Reynolds number turbulent ferrofluid pipe flow experiments described previously [K. R. Schumacher, Phys. Rev. E 67, 026308 (2003)].


Development of a Psychological Scale for Measuring Disruptive Clinician Behavior.
Disruptive clinician behavior worsens communication, information transfer, and teamwork, all of which negatively affect patient safety. Improving safety in medical care requires an accurate assessment of the damage caused by disruptive clinician behavior. Psychometric scales complement case reports, but existing scales have significant limitations. Therefore, this study developed a psychometric scale based on the psychological paradigm to assess disruptive clinician behavior. The scale was developed through a sequence of steps. First, we used an open-ended questionnaire targeting 712 nurses, content analysis, and content validity assessment by 5 experts to determine valid items for disruptive clinical behavior. Next, an Internet questionnaire survey targeting 1000 health care staff, exploratory factor analysis, and subfactor analysis was conducted to identify necessary and sufficient factors. Then, we calculated difficulty level and discriminative power. We also conducted a field questionnaire survey targeting 84 staff in a hospital. Finally, we calculated ω coefficients and then used confirmatory factor analysis to verify the fit of the hypothesized model. Our open-ended survey involving 478 nurses identified 47 codes in 9 categories. The questionnaire survey involving hospital 1000 medical staff identified 6 factors, with 1 factor subdivided into 4 subfactors and 1 into 2 subfactors. The goodness of fit of the hypothesized 10-factor models with factor pairs and groups was confirmed. We developed a psychometric scale measuring subjective assessments of harm covering various disruptive clinician behaviors. The scale complements interviews and case reports by generating valid, reliable scores for various disruptive clinician behaviors in health care institutions.


Core Microbiota in Central Lung Cancer With Streptococcal Enrichment as a Possible Diagnostic Marker.
Dysbiosis in lung cancer has been underexplored. The aim of this study was to define the bacterial and fungal microbiota of the bronchi in central lung cancer and to compare it with that of the oral and intestinal compartments. Twenty-five patients with central lung cancer and sixteen controls without antimicrobial intake during the previous month were recruited. Bacterial and fungal distribution was determined by massive sequencing of bronchial biopsies and saliva and faecal samples. Complex computational analysis was performed to define the core lung microbiota. Affected and contralateral bronchi of patients have almost identical microbiota dominated by Streptococcus, whereas Pseudomonas was the dominant genera in controls. Oral and pulmonary ecosystems were significantly more similar in patients, probably due to microaspirations. Streptococcal abundance in the bronchi differentiated patients from controls according to a ROC curve analysis (90.9% sensitivity, 83.3% specificity, AUC=0.897). The saliva of patients characteristically showed a greater abundance of Streptococcus, Rothia, Gemella and Lactobacillus. The mycobiome of controls (Candida) was significantly different from that of patients (Malassezia). Cancer patients' bronchial mycobiome was similar to their saliva, but different from their contralateral bronchi. The central lung cancer microbiome shows high levels of Streptococcus, and differs significantly in its composition from that of control subjects. Changes are not restricted to tumour tissue, and seem to be the consequence of microaspirations from the oral cavity. These findings could be useful in the screening and even diagnosis of this disease.


Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center.
The currently available indication criteria of living donor liver transplantation (LDLT) for patients with hepatocellular carcinoma (HCC) have high prognostic power but insufficient discriminatory power. On the basis of single-center results from 221 HCC patients undergoing LDLT, we modified the indication criteria for LDLT to expand recipient selection without increasing the posttransplant recurrence of HCC. Our expanded criteria, based on explant pathology, were largest tumor diameter < or = 5 cm, HCC number < or = 6, and no gross vascular invasion. One hundred eighty-six of the 221 HCC patients (84.2%) met our criteria, 10% and 5.5% more than those that met the Milan and University of California at San Francisco (UCSF) criteria, respectively. The overall 5-year patient survival rates were 76.0% and 44.5% within and beyond the Milan criteria, respectively; 75.9% and 36.4% within and beyond the UCSF criteria, respectively; and 76.3% and 18.9% within and beyond our expanded criteria, respectively. Although these 3 sets of criteria had similar prognostic power, our expanded criteria had the highest discriminatory power. Thus, these expanded criteria for LDLT eligibility of HCC patients broaden the indications for patient selection and can more accurately identify patients who will benefit from LDLT.


Unusual structures in single-stranded ribonucleic acid: proton nuclear magnetic resonance of AUCCA in deuterium oxide.
Conformational features of the oligoribonucleic acid (oligo-RNA) A1-U2-C3-C4-A5 are explored by proton nuclear magnetic resonance (NMR). The sequence is a molecular cognate of a portion of the T psi C loop and stem regions of yeast tRNAPhe. The molecule forms at least two classes of flexible yet ordered structures. Class I states are similar in spectral properties to the component oligomers, AU, AUC, and AUCC, and are likely to be standard right-helical structures. Class II states are characterized by a 2'-endo pucker at A1 and unusually large shielding of several C3 and U2 protons. Most of these features are consistent with identifying the class II solution structures with the "arch" conformation for the T psi C region determined by X-ray crystallography of yeast tRNAPhe.


Effects of several sea anemone and scorpion toxins on excitability and ionic currents in the giant axon of the cockroach.
The membrane effects of 4 sea anemone and 6 scorpion toxins have been studied under current clamp and voltage clamp conditions. Micromolar concentrations of the purified toxins were applied externally on single giant axons of the american cockroach. Periplaneta americana in a double oil-gap arrangement and the effects on the resting potential, action potential and underlying currents analysed. The 4 sea anemone toxins (Condylactis toxin, Anemonia toxin 2, Anthopleurin toxin A and Parasicyonis toxin) were found to considerably prolong the action potential. This effect is frequency dependent and long plateau spikes (100-500 ms in duration) are consistently seen for frequencies lower than 0.2 Hz. This effect is due to a considerable delay in the turning-off of the sodium current during square membrane depolarizations associated, for large concentrations, with a decrease in the potassium conductance. Toxin effects on the sodium current are not prevented by pretreatment with STX. From the 4 purified toxins extracted from the venom of the scorpion, Androctonus australis Hector, 3 (Mammal toxins 1 and 2 and crustacean toxin) were found to have sea anemone toxin like effects and to induce long duration plateau action potentials. As for sea anemone toxins, this effect is due to a lengthening of the falling phase of the sodium current associated with a small decrease in the potassium conductance. The 4th toxin (insect toxin or ITAaH) depolarizes the membrane and induces repetitive firing of short action potentials.(ABSTRACT TRUNCATED AT 250 WORDS)


Signals governing monocyte differentiation during inflammation.
Monocytes are innate immune cells that develop in the bone marrow and are continually released into circulation, where they are poised to enter tissues in response to homeostatic or inflammatory cues. Monocytes are highly plastic cells that can differentiate in tissues into a variety of monocyte-derived cells to replace resident tissue macrophages, promote inflammatory responses, or resolution of inflammation. As such, monocytes can support tissue homeostasis as well as productive and pathogenic immune responses. Recent work shows previously unappreciated heterogeneity in monocyte development and differentiation in the steady state and during infectious, autoimmune, and inflammatory diseases. Monocyte-derived cells can differentiate via signals from cytokines, pattern recognition receptors or other factors, which can influence development in the bone marrow or in tissues. An improved understanding of these monocyte-derived cells and the signals that drive their differentiation in distinct inflammatory settings could allow for targeting these pathways in pathological inflammation.


Development and psychometric testing of the Organizational Silence Behavior Scale for healthcare professionals.
Organizational silence maintained by professionals working in the healthcare sector could result in various moral dilemmas and might negatively affect patient care. The aim of this methodological study was to develop a scale that measured the organizational silence behaviors of healthcare professionals. During the development of the scale, researchers conducted in-depth interviews with 30 healthcare professionals in order to create a draft pool of 66 scale items. After content validity, a 62 item scale was drafted. In the second stage of development, psychometric properties of the scale were evaluated. The results of the confirmatory factor analysis indicated that adequate fit indices (χ2 value to degrees of freedom = 3.54; goodness-of-fit index = .92; root mean square error of approximation = .90) were achieved and resulted in a 32 item scale with four subscales. These subscales were assessed using a 5 point Likert scale. The Cronbach's alpha for the scale was .93, and for the subscales, it was as follows: silence climate: α = .91, silence based on fear: = .91, acquiesce silence: α = .93, and silence based on protecting the organization: α = .85. The Organizational Silence Behavior Scale was successfully developed and showed satisfactory validity and reliability. It is usable among healthcare professionals.


The clinical efficacy of autogenous dentin blocks prepared chairside for alveolar ridge augmentation: A systematic review and meta-analysis.
This systematic review aimed to evaluate the current evidence on the effectiveness of autogenous dentin block graft prepared chairside for alveolar ridge augmentation and compare its clinical outcomes to the main available grafting materials and techniques. Three databases were screened, including prospective clinical studies, utilizing autogenous dentin blocks for ridge augmentation, with at least 3 months of postoperative follow-up. Eight articles were included, and four of them were meta-analyzed. Dentin blocks demonstrated similar vertical bone gain and significantly higher width gain, compared to bone blocks (WMD = 0.03, 95% CI -0.51 to 0.57, p = .92 and WMD = 1.34, 95% CI 0.57 to 2.12, p = .0007, respectively). Vertical and horizontal resorption were similar between the two groups (WMD = -0.36, 95% CI -0.91 to 0.18, p = .19, and WMD = -0.47, 95% CI -1.05 to 0.11, p = .11, respectively). Dentin blocks showed more incidences of postoperative complications, however, with no statistical significance (RR = 4.30, 95% CI 0.97 to 18.96, p = .054). The need for additional augmentation upon implant placement was also similar between both grafts (RR = 0.95, 95% CI 0.39 to 2.28, p = .90). Recorded incidences of graft exposure were low (2.27%), and no study stated surgical site infection. Within its limitations, this study indicates that the autogenous dentin blocks prepared chairside could be a possible alternative to the other established bone augmentation techniques for staged ridge augmentation. Nevertheless, future studies are needed to confirm its efficacy and implant success/survival in sites grafted with this material.


Long-term effects of pancreas transplant alone on nephropathy in type 1 diabetic patients with optimal renal function.
Limited data are available regarding optimal selection criteria for pancreas transplant alone (PTA) to minimize aggravation of diabetic nephropathy. A total of 87 type 1 diabetic patients were evaluated before and after PTA at a single center from January, 1999 to December, 2015, together with 87 matched non-transplanted type 1 diabetic subjects who were candidates for PTA to compare deterioration of native kidney function. A total of 163 patients (79 in the transplanted group and 84 in the nontransplanted group) were finally enrolled after excluding nine patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m2 and two patients with moderate proteinuria (≥ 1.5 g/day). A total of seven recipients (8.9%) had end-stage renal disease post-transplant whereas only one patient (1.2%) developed end-stage renal disease in the nontransplanted group during their follow-up period (median 12.0, range 6-96 months) (p = 0.03). Furthermore, a composite of severe renal dysfunction and end-stage renal disease (31.6% vs 2.4%) was significantly higher in the transplanted group (p < 0.001). Multivariate Cox regression analysis revealed that a higher level of tacrolimus at six months post-transplant (HR = 1.648, CI = 1.140-2.385, p = 0.008) was the only significant factor associated with end-stage renal disease. There is a considerable risk for deterioration of renal function in PTA recipients post-transplant compared with non-transplant diabetic patients. With rather strict selection criteria such as preoperative proteinuria and estimated glomerular filtration rate, PTA should be considered in diabetic patients to minimize post-transplant aggravation of diabetic nephropathy.


The specific NQO2 inhibitor, S29434, only marginally improves the survival of dopamine neurons in MPTP-intoxicated mice.
Over the years, evidence has accumulated on a possible contributive role of the cytosolic quinone reductase NQO2 in models of dopamine neuron degeneration induced by parkinsonian toxin, but most of the data have been obtained in vitro. For this reason, we asked the question whether NQO2 is involved in the in vivo toxicity of MPTP, a neurotoxin classically used to model Parkinson disease-induced neurodegeneration. First, we show that NQO2 is expressed in mouse substantia nigra dopaminergic cell bodies and in human dopaminergic SH-SY5Y cells as well. A highly specific NQO2 inhibitor, S29434, was able to reduce MPTP-induced cell death in a co-culture system of SH-SY5Y cells with astrocytoma U373 cells but was inactive in SH-SY5Y monocultures. We found that S29434 only marginally prevents substantia nigra tyrosine hydroxylase+ cell loss after MPTP intoxication in vivo. The compound produced a slight increase of dopaminergic cell survival at day 7 and 21 following MPTP treatment, especially with 1.5 and 3 mg/kg dosage regimen. The rescue effect did not reach statistical significance (except for one experiment at day 7) and tended to decrease with the 4.5 mg/kg dose, at the latest time point. Despite the lack of robust protective activity of the inhibitor of NQO2 in the mouse MPTP model, we cannot rule out a possible role of the enzyme in parkinsonian degeneration, particularly because it is substantially expressed in dopaminergic neurons.


Magnetic polarization effects of temperature sensors and heaters in LISA Pathfinder.
Temperature sensors and heaters belong in the diagnostics subsystem of the LISA Technology Package (LTP) on board LISA Pathfinder, the technology demonstrator for LISA. A number of these diagnostics items are placed at short distances from the LTP proof masses and are negative temperature coefficient (NTC) thermistors. By design, these devices have tiny amounts of ferromagnetic materials, which therefore constitute a potential source of disturbance to the performance of the LTP. In this paper we report on detailed magnetic characterization of the NTCs and use the data to evaluate their impact on the acceleration noise budget of the LTP. The effect is seen to be small if the NTCs are submitted to a demagnetization process before they are attached. Remagnetization is unlikely, as rather strong fields (approximately millitesla) are required to produce enough NTC magnetic polarization.


Immunohistochemical fiber typing of harbor seal skeletal muscle.
There is strong evidence that pinnipeds maintain a lipid-based, aerobic metabolism during diving. However, the few fiber-typing studies performed on pinniped skeletal muscles are not consistent with an aerobic physiological profile. The objective of this study was to reexamine the fiber type distribution throughout the primary locomotory muscles of the harbor seal Phoca vitulina. Results from immunohistochemical (IHC) fiber typing indicated that harbor seal swimming muscles (the epaxial muscles) are composed of 47.4% type I (slow twitch, oxidative) fibers and 52.8% IIa (fast twitch, oxidative) fibers, which are homogeneously distributed throughout the muscle. Harbor seal pectoralis, a secondary swimming muscle, was composed of 16.2% type I and 84.3% type IIa fibers. No fast twitch, glycolytic (type IIb) fibers were detected in either muscle, in contrast to published data on fiber typing of harbor seal epaxial muscles using traditional histochemical techniques. The extreme specificity inherent in the IHC fiber typing procedure leads us to conclude that harbor seal swimming muscle is entirely composed of oxidative fibers. Our results are consistent with the enzymatic analyses of pinniped skeletal muscle that support the use of lipid-derived aerobic catabolism to fuel working muscle during diving in these marine mammals.


Specificity of adoptive chemoimmunotherapy of established syngeneic tumors.
To examine the specificity of adoptive chemoimmunotherapy (ACIT) of established syngeneic tumors, two noncross-reactive C57BL/6 tumors were studied: a Friend virus-induced tumor (FBL-3) and a chemically induced virus-negative tumor EL-4(G-). In vitro studies confirmed that these tumors are antigenically distinct by demonstrating that the cytotoxic responses of spleen cells from mice immunized in vivo and reexposed to tumor in vitro are immunologically specific. Studies of ACIT with cells from mice immunized in vivo demonstrated similar specificity. Mice receiving 5 x 10(6) FBL-3 on day 0 all died by day 13. Treatment on day 5 with cyclophosphamide (CY), 180 mg/kg, prolonged the median survival time (MST) to day 23. Treatment on day 5 with CY plus 2 x 10(7) normal nonimmune C57BL/6 cells or CY plus cells sensitized to EL-4(G-) had no additional effect on survival whereas 2 x 10(7) C57BL/6 cells sensitized to FBL-3 in vivo prolonged MST to day 64 and cured 13 of 32 mice. Similarly, mice given 2 x 10(5) EL-4(G-) on day 0 all died by day 16, and CY on day 5 prolonged the MST to day 22. As an adjunct to CY, 2 X 10(7) normal cells or cells sensitized to FBL-3 had a modest effect, prolonging the MST to days 37 and 36, respectively. However, treatment with CY plus 2 x 10(7) cells immune to EL-4(G-) cured 22 of 32 mice. The results demonstrate the immunologic specificity of ACIT of syngeneic tumors treated with immune syngeneic cells.


Trained Cohorts of University Students are a Useful Resource for Conducting Dietary Surveys in Mongolia.
Population-based dietary assessment is important for informing national nutrition policy. The developing country setting presents challenges for robust implementation of dietary surveys, yet effective nutrition interventions are often urgently required. To develop and evaluate a low-cost approach to epidemiologic dietary assessment in Mongolia, involving the use of large cohorts of local public health and medical students as research assistants for collecting diet records. From 2011 to 2016, over 200 Mongolian medical and public health university students were trained to collect paired summer and winter 3-day weighed diet records from urban and rural study populations across the geographic expanse of Mongolia. Students were supervised during data collection, and their performance and experience during training and data collection were qualitatively evaluated from their own perspectives as well as those of the investigators. Students collected detailed and thorough diet records and generally reported positive feedback regarding training and data collection. Frequent supervision of students during data collection proved to be extremely worthwhile. While rural participants were amenable to having students follow them, students faced several challenges in assessing the diets of urban participants. These challenges may best be addressed by separately training these participants beforehand. With adequate training and supervision, university students may be a useful and cost-effective resource for large-scale dietary surveys in regions where their use would be practical and culturally appropriate. Further research is warranted to study how well this approach may be adapted outside Mongolia and to other dietary assessment methods and technologies.


REWRITING ECOLOGICAL SUCCESSION HISTORY: DID CARRION ECOLOGISTS GET THERE FIRST?
Ecological succession is arguably the most enduring contribution of plant ecologists and its origins have never been contested. However, we show that French entomologist Pierre Mégnin, while collaborating with medical examiners in the late 1800s, advanced the first formal definition and testable mechanism of ecological succession. This discovery gave birth to the twin disciplines of carrion ecology and forensic entomology. As a novel case of multiple independent discovery, we chronicle how the disciplines of plant and carrion ecology (including forensic entomology) accumulated strikingly similar parallel histories and contributions. In the 1900s, the two groups diverged in methodology and purpose, with carrion ecologists and forensic entomologists focusing mostly on case reports and observational studies instead of hypothesis testing. Momentum is currently growing, however, to develop the ecological framework of forensic entomology and advance carrion ecology theory. Researchers are recognizing the potential of carcasses as subjects for testing not only succession mechanisms (without assuming space-for-time substitution), but also aggregation and coexistence models, diversity-ecosystem function relationships, and the dynamics of pulsed resources. By comparing the contributions of plant and carrion ecologists, we hope to stimulate future crossover research that leads to a general theory of ecological succession.


Hypercortisolism and insulin resistance: comparative effects of prednisone, hydrocortisone, and dexamethasone on insulin binding of human erythrocytes.
We have studied the effects of 3 days of hydrocortisone (30 mg every 8 h), dexamethasone (1 mg every 8 h), and prednisone (7.5 mg every 8 h) ingestion on glucose intolerance and insulin resistance in three groups of lean normal volunteers and compared these parameters to specific insulin binding in erythrocytes. All three glucocorticoids caused significant reduction of glucose tolerance as assessed by glucose and insulin areas under oral glucose tolerance text curves and insulin sensitivity in response to 0.1 U insulin/kg BW, iv. Although both hydrocortisone and dexamethasone caused significant reduction in insulin binding compared to that during the pretreatment period (11.0 +/- 0.7 vs. 9.0 +/- 0.5% (P less than 0.01) and 11.8 +/- 0.7 vs. 9.0 +/- 0.5% (P less than 0.05), respectively), prednisone ingestion did not significantly alter insulin binding (10.6 +/- 0.6 before vs. 9.4 +/- 0.5% after). Decreased insulin binding with hydrocortisone and dexamethasone was caused by decreased binding affinity rather than by a decreased number of receptors. In two subjects in whom receptor binding was measured daily for 3 days during prednisone (one subject) or hydrocortisone (one subject) ingestion, the inhibition of binding was highest on the first day, with subsequent reduction of this inhibited binding toward normal by the third day. We conclude that although hydrocortisone, dexamethasone, and prednisone all cause deterioration of glucose tolerance and decreased insulin sensitivity, only hydrocortisone and dexamethasone exhibit significant decreases in insulin binding to erythrocytes. This decreased binding is not due to changes in receptor numbers but to decreased affinity brought about by hyperinsulinemia. Prednisone ingestion caused significant insulin resistance with an insignificant decrease in insulin binding. We believe that other mechanisms, such as alteration of postreceptor events, may play a major role in the induction of insulin resistance in hypercortisolism in man.


MicroRNA expression in inflamed and noninflamed gingival tissues from Japanese patients.
Periodontitis is a chronic inflammatory disease caused by specific bacteria and viruses. Local, systemic, and environmental factors affect the rate of disease progression. Immune responses to bacterial products, and the subsequent production of inflammatory cytokines, are crucial in the destruction of periodontal tissue. MicroRNAs (miRNAs) are a class of small RNAs that control various cell processes by negatively regulating protein-coding genes. In this study, we compared miRNA expression in inflamed and noninflamed gingival tissues from Japanese dental patients. Total RNAs were isolated from inflamed and noninflamed gingival tissues. miRNA expression profiles were examined by an miRNA microarray, and the data were analyzed by GeneSpring GX, Ingenuity Pathways Analysis, and the TargetScan databases. Observed miRNA expression levels in inflamed gingiva were confirmed by real-time PCR. The three most overexpressed (by >2.72-fold) miRNAs were hsa-miR-150, hsa-miR-223, and hsa-miR-200b, and the three most underexpressed (by <0.39-fold) miRNAs were hsa-miR-379, hsa-miR-199a-5p, and hsa-miR-214. In IPA analysis, hsa-miR-150, hsa-miR-223, and hsa-miR-200b were associated with inflammatory disease, organismal injury, abnormalities, urological disease, and cancer. The present findings suggest that miRNAs are associated with chronic periodontitis lesions in Japanese.


Heavy metal phyto-accumulation in leafy vegetables irrigated with municipal wastewater and human health risk repercussions.
In this study, heavy metal phyto-accumulation potential of selected cultivars of two leafy vegetables on irrigation with municipal wastewater and human health risks were investigated. Municipal wastewater chemistry was recorded significantly different from groundwater control and led to the two-fold high enrichment of soil heavy metal contents (Ni, 19.46; Pb, 23.94; Co, 4.68; Cd, 1.4 in mg/kg, respectively). Interactive effects for phyto-accumulation of most heavy metals were also recorded significant at p < 0.001 in four vegetable cultivars. Heatmap revealed higher accumulation of heavy metals (Fe, Zn, Mn, Cu, Pb, Cr, Co) in spinach cultivars than lettuce cultivars creating elevated health risk index (HRI) and hazard index (HI) values for adults and children. Highest HI was recorded for Lahori palak (adults, 1.42; children, 2.58) and lowest for iceberg (adults, 0.04; children, 0.07). The NPK supplementation improved mineral composition of leafy vegetables within safer human health limits in control treatments. However, in municipal wastewater treatments, NPK fertilization decreased heavy metal uptake and phyto-accumulation in S2 (Lahori palak) than remaining vegetable cultivars leading to reduced health risk values. Because of higher heavy metal phyto-accumulation and health risks, cultivation of spinach cultivars must be discouraged in agro-ecologies receiving municipal wastes, whereas lettuce cultivars should be promoted.


Imidazole and imidazolate iron complexes: on the way for tuning 3D-structural characteristics and reactivity. Redox interconversions controlled by protonation state.
X-ray structures for six Fe(II) and Fe(III) complexes from two closely heptadentate N-tripodal ligands, L1H(3) = tris[(imidazol-4-yl)-3-aza-3-butenyl]amine and L2H(3) = tris[(imidazol-2-yl)-3-aza-3-butenyl]amine, are described: three complexes in the L1 series (namely, [Fe(II)(L1H(3))](2+) and [Fe(III)(L1H(3))](3+) at low pH and [Fe(III)(L1)](0) at high pH) and three complexes in the L2 series (namely, [Fe(II)(L2H(3))](2+) at low pH and [Fe(II)(L2H)](0) and [Fe(III)(L2)](0) at high pH). Most of these complexes are stable in both Fe(II) and Fe(III) redox states and with the ligand in various protonation states. In the solid state, hydrogen bonds networks were obtained. Structural differences induced by 2- or 4-imidazole substitution are described and discussed. In solution, interconversions between different forms, with regard to oxidation and protonation states, were investigated by UV-visible spectroscopy, cyclic voltammetry, and potentiometry. The deprotonation pattern of these polyimidazole iron(II) and iron(III) complexes is described in detail. pK(a)s of the imidazolate/imidazole moieties in MeOH/H(2)O are reported. Two new species, namely, [Fe(II)(L1)](-) and [Fe(II)(L2)](-), were shown to be obtained in DMSO upon strong base addition and characterized by UV-vis spectroscopy and cyclic voltammetry. Half-wave potentials of Fe(III)/Fe(II) complexes with ligand moieties in several protonation states are reported, both in DMSO and in MeOH/H(2)O. Because of the presence of free imidazole groups coordinated to the iron, the potential of the iron(III)/iron(II) couples can be tuned by pH. A shift of DeltaE = E(deprot) - E(prot) ranging from -270 to -320 mV per exchanged proton in DMSO was measured. This study shows moreover that interconversions (with regard to both redox and protonation states) can be reversed several times. As the complexes have been isolated in order to be tested as superoxide dismutase mimics, preliminary reactions with dioxygen and with superoxide, considered as oxidant and reducer of biological importance, are reported. In these two series, O(2)(-) behaves either as a base or as a reducer and no adducts have been observed.


Tolerance and efficacy of tribasic manganese chloride in growing broiler chickens.
These studies were designed to determine the relative bioavailability and tolerance of tribasic Mn chloride (TBMC) for growing broiler chickens. In experiment 1, birds were fed a basal diet (starter, 102 ppm; grower, 209 ppm) or the basal diet supplemented with 3,600, 4,500, or 5,400 ppm Mn from either TBMC or manganese sulfate (MnSO(4)), and BW, feed intake, and plasma Mn were measured. In experiments 2 and 3, diets included the basal diet (45 and 43 ppm Mn, respectively) and the basal diet supplemented with graded levels of either TBMC or MnSO(4) ranging from 30 to 240 ppm Mn. Body weight and feed intake were measured and tibia, bile, and liver were collected for mineral analysis; heart samples were taken for manganese superoxide dismutase activity, protein, and relative mRNA abundance. In experiment 1, BW differed among treatments, with higher Mn leading to lower BW (P < 0.05). Birds from all treatments showed higher plasma Mn than birds fed the basal diet. Birds supplemented with the highest level of MnSO(4) had the highest level of plasma Mn (P < 0.05). In experiment 2, tibia and liver Mn increased with higher dietary Mn regardless of source (P < 0.05). Liver Mn increased up to the 60 ppm diets whereas Mn in the tibia was highest with the 130 ppm diets. Bile Mn increased with increasing dietary Mn, but these differences were not significant. In experiment 3, manganese superoxide dismutase activity, protein, and relative mRNA abundance were not affected by diet. The calculated bioavailabilities of TBMC and MnSO(4) did not differ significantly (P > 0.20). Together, these results indicate that TBMC is as effective as and better tolerated than MnSO(4) and that supplementing Mn at the lowest level used in this study may be sufficient for normal development of broiler chickens.


The Difficult Gallbladder: A Safe Approach to a Dangerous Problem.
Laparoscopic cholecystectomy is a common surgical procedure, and remains the gold standard for the management of benign gallbladder and biliary disease. While this procedure can be technically straightforward, it can also represent one of the most challenging operations facing surgeons. This dichotomy of a routine operation performed so commonly that poses such a hidden risk of severe complications, such as bile duct injury, must keep surgeons steadfast in the pursuit of safety. The "difficult gallbladder" requires strict adherence to the Culture of Safety in Cholecystectomy, which promotes safety first and assists surgeons in managing or avoiding difficult operative situations. This review will discuss the management of the difficult gallbladder and propose the use of subtotal fenestrating cholecystectomy as a definitive option during this dangerous situation.


Development of a novel high power sub-THz second harmonic gyrotron.
Record-breaking high power coherent radiation at a subterahertz frequency region from a gyrotron utilizing second harmonic resonance modes was attained with a simple cavity. In order to aim at high power and high frequency simultaneously, the oscillation mode was selected carefully enough to realize stable radiation free from mode competition. The cavity radius was determined from the viewpoints of the oscillation frequency, the coupling coefficient between the electron beam, and the rf-electric field. The cavity length was also optimized for the highest perpendicular efficiency. In addition, a new electron gun which is capable of generating a thin laminar beam for a large current was introduced. Consequently, single mode second harmonic radiation with powers of 52 and 37 kW at frequencies of about 349 and 390 GHz, respectively, was achieved.


IL-33 priming regulates multiple steps of the neutrophil-mediated anti-Candida albicans response by modulating TLR and dectin-1 signals.
IL-33 is known to play an important role in Th2 immunity. In this study, we investigated the effect of IL-33 pretreatment on anti-fungal response using an acute Candida albicans peritoneal infection model. IL-33 pretreatment induced a rapid fungal clearance and markedly reduced the C. albicans infection-associated mortality. The priming effect of IL-33 occurred during multiple steps of the neutrophil-mediated anti-fungal response. First, the anti-fungal effect occurred due to the rapid and massive recruitment of neutrophils to the site of infection as a result of the release of CXCR2 chemokines by peritoneal macrophages and by reversal of the TLR-induced reduction of CXCR2 expression in neutrophils during IL-33 priming. Second, conditioning of neutrophils by IL-33 activated the TLR and dectin-1 signaling pathways, leading to the upregulation of complement receptor 3 expression induced by C. albicans. Upregulated CR3 in turn increased the phagocytosis of opsonized C. albicans and resulted in the production of high levels of reactive oxygen species and the subsequent enhanced killing activity of neutrophils. Taken together, our results suggest that IL-33 can regulate the anti-fungal activity of neutrophils by collaborative modulation of the signaling pathways of different classes of innate immune receptors.


Life cycle analysis of unicellular algae.
Unicellular green alga is a very convenient object for flow cytometric characterization. Flow cytometry has been proposed as a quick and reliable tool for studying life cycle and growth of unicellular algae. Cell size of vegetating algae can be monitored in association with their DNA and endogenous chlorophyll content. Cells of interest (e.g., group of cells of a certain stage of the life cycle) in an asynchronously proliferating cell population can be sorted out for further microscopical or molecular biology studies. This methodological approach can be helpful for researchers who are interested in algal proliferation.


Volatile anaesthetic myocardial protection: a review of the current literature.
Ischaemic preconditioning is a powerful innate adaptive phenomenon whereby brief periods of sublethal ischaemia result in marked tolerance to subsequent lethal ischaemia. Halogenated anaesthetics have been shown to mimic ischaemic preconditioning, modifying and attenuating ischaemia reperfusion injury. This review aims to present the current animal and human data, discuss the possible mechanisms of action and review the clinical evidence for volatile anaesthetic-induced myocardial protection. There is class Ia evidence for the myocardial protective properties of sevoflurane and desflurane in low risk patients undergoing coronary artery bypass grafting surgery. These volatile anaesthetics have been shown to improve clinical outcomes and health economics following cardiac surgery, reducing intensive care and hospital stay. The evidence for the benefit of volatile anaesthetics in non-cardiac surgery is less robust and further large randomized controlled trials are required to elucidate this question.


A Case of Primary Bacterial Pericarditis with Recurrent Cardiac Tamponade.
Cardiac tamponade is an important and potentially lethal complication of acute pericarditis. However, recurrence of cardiac tamponade is rare when it is treated appropriately. We present a 49-year-old man with bacterial pericarditis and recurrent cardiac tamponade, which was caused by the rupture of an upper part of the left atrium (LA). According to the autopsy findings, bacteremia from Staphylococcus aureus developed on a substrate of poorly controlled diabetes mellitus and spread to the pericardium via the blood. Subsequently, tissue necrosis developed from the pulmonary trunk and aorta to the LA, leading to recurrence of cardiac rupture and cardiac tamponade.


Multianalyte chemical identification and quantitation using a single radio frequency identification sensor.
We demonstrate an approach for multianalyte chemical identification and quantitation using a single conventional radio frequency identification (RFID) tag that has been adapted for chemical sensing. Unlike other approaches of using RFID sensors, where a special tag should be designed at a much higher cost, we utilize a conventional RFID tag and coat it with a chemically sensitive film. As an example, we demonstrate detection of several vapors of industrial, health, law enforcement, and security interest (ethanol, methanol, acetonitrile, water vapors) with a single 13.56-MHz RFID tag coated with a solid polymer electrolyte sensing film. By measuring simultaneously several parameters of the complex impedance from such an RFID sensor and applying multivariate statistical analysis methods, we were able to identify and quantify several vapors of interest. With a careful selection of the sensing film and measurement conditions, we achieved parts-per-billion vapor detection limits in air. These RFID sensors are very attractive as ubiquitous multianalyte distributed sensor networks.


Cognitive and behavioral aspects of executive functions in children born very preterm.
This study investigated whether children aged between 8 and 12 years born very preterm (VPT) and/or at very low birth weight (VLBW) performed lower than same-aged term-born controls in cognitive and behavioral aspects of three executive functions: inhibition, working memory, and shifting. Special attention was given to sex differences. Fifty-two VPT/VLBW children (26 girls, 50%) born in the cohort of 1998-2003 and 36 same-aged term-born children (18 girls, 50%) were recruited. As cognitive measures, children completed tasks of inhibition (Color-Word Interference Test, D-KEFS; Delis, Kaplan, & Kramer, 2001), working memory (digit span backwards, HAWIK-IV; Petermann & Petermann, 2008), and shifting (Trail Making Test, number-letter-switching, D-KEFS; Delis et al., 2001). As behavioral measures, mothers completed the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000). Scales of interest were inhibit, working memory, and shift. Analyses of the cognitive aspects of executive functions revealed that VPT/VLBW children performed significantly lower than controls in the shifting task but not in the working memory and inhibition tasks. Analyses of behavioral aspects of executive functions revealed that VPT/VLBW children displayed more problems than the controls in working memory in everyday life but not in inhibition and shifting. No sex differences could be detected either in cognitive or behavioral aspects of executive functions. To conclude, cognitive and behavioral measures of executive functions were not congruent in VPT/VLBW children. In clinical practice, the combination of cognitive and behavioral instruments is required to disclose children's executive difficulties.


Photochemical instability of thiol-capped CdTe quantum dots in aqueous solution and living cells: process and mechanism.
The process and mechanism of photochemical instability of thiol-capped CdTe quantum dots (QDs) in aqueous solution were experimentally studied. After laser irradiation, the corresponding Raman bands of the Cd-S bond decreased obviously, indicating bond breaking and thiol detachment from the QD surfaces. Meanwhile, a photoinduced aggregation of QDs occurred with the hydrodynamic diameter <Dh> increased to hundreds of nanometers from an initial 20 nm, as detected with dynamic light scattering measurements. The bleaching of the photoluminescence of QDs under laser irradiation could be attributed to the enhanced nonradiative transfer in excited QDs caused by increased surface defects due to the losing of thiol ligands. Singlet oxygen (1O2) was involved in the photooxidation of QDs, as revealed by the inhibiting effects of 1O2 quenchers of histidine or sodium azide (NaN3) on the photobleaching of QDs. The linear relationship in Stern-Volmer measurements between the terminal product and the concentration of NaN3 demonstrated that 1O2 was the main pathway of the photobleaching in QD solutions. By comparing the photostability of QDs in C2C12 cells with and without NaN3 treatment, the photooxidation effect of 1O2 on photobleaching of cellular QDs was confirmed.


Intrauterine insemination versus fallopian tube sperm perfusion for non tubal infertility.
Controlled ovarian hyperstimulation (COH) together with intrauterine insemination (IUI) is commonly offered to couples with infertility factors not involving the fallopian tubes. Intrauterine insemination gained its popularity because it is simple, non-invasive and cost-effective technique. Another simple non invasive method was introduced called fallopian tube sperm perfusion (FSP). This technique was developed to ensure the presence of higher sperm densities in the fallopian tubes at the time of ovulation than standard IUI provides. Fallopian tube sperm perfusion is based on pressure injection of 4 ml of sperm suspension with attempt of sealing of the cervix to prevent semen reflux. The IUI technique on the other hand is based on intrauterine injection of 0.5 ml of sperm suspension without flushing the tubes. A number of randomised controlled trials have been published comparing the efficacy of FSP with standard IUI. There were considerable variations in the results. The aim of this review was to determine whether outcomes differ between FSP and IUI in improving the probability of conception. To investigate whether outcomes differ between fallopian tube sperm perfusion and intrauterine insemination in the treatment of non tubal subfertility resulting in pregnancies and live births. We searched the Menstrual Disorders & Subfertility Group trials register (24 March 2003), MEDLINE (January 1966 to July 2003) and EMBASE (January 1988 to July 2003). Abstracts of the American Society for Reproductive Medicine (1987 to 2003) and European Society for Human Reproduction and Embryology (1987 to 2003) meetings were searched with the same key- or text words. Only randomised controlled studies comparing fallopian tube sperm perfusion with intrauterine insemination were included in this review. The method of allocation was assessed to determine whether each study was truly randomised or pseudo-randomised. Only first period data of cross-over trials were included for analysis. Couples who have been trying to conceive for at least one year were included but only when the female partner had patent tubes. Two independent reviewers (AC and MJ) selected the trials for inclusion based on the quality of the studies. Overall six studies involving 474 couples were included in the meta-analysis. Only one study assessed live birth rates (OR 1.17, 95% CI 0.39 3.53). The results for pregnancy rate per couple were statistically significant with FSP showing higher pregnancy rates (OR 1.85, 95% CI 1.23 to 2.79 using the odds ratio with the fixed effect model. To check the results the random effect model was used, which gave a wider confidence interval which crossed the line of no significance (OR 1.76, 95% CI 0.77 to 4.05). As a result, these outcomes should be interpreted with caution. Subgroup analysis revealed that couples suffering from unexplained subfertility benefit from FSP over IUI, resulting in significantly higher pregnancy rates (OR 2.88, 95% CI 1.73 to 4.78). Excluding studies which used the Foley catheter for tubal perfusion resulted in a significant difference favouring FSP for all indications (OR 2.42, 95% CI 1.54 to 3.80). FSP may be more effective for non-tubal subfertility, but the significant heterogeneity should be taken into account. As a result no advice based on the meta-analysis could be given for the treatment of non-tubal subfertility. Subgroup analysis, which did not show evidence of statistical heterogeneity, suggested that couples with unexplained infertility may benefit from FSP over IUI in terms of higher pregnancy rates. FSP may therefore be advised in couples with unexplained subfertility. Results suggested the possibility of differential effectiveness of FSP depending on catheter choice.


Usage of positional therapy in adults with obstructive sleep apnea.
Many positional therapy (PT) strategies are available for treating positional obstructive sleep apnea (OSA). PT is primarily supplied to selected patients as a secondary treatment option when other therapies have failed. To our knowledge this is the largest study to date to assess effectiveness and long-term compliance of PT (both commercial waistband and self-made constructions, mimicking the tennis ball technique) as primary treatment in patients with different positional OSA severities. PT was used by 53 patients, of which 40 patients underwent a follow-up polygraphic evaluation under treatment after a median time interval of 12 weeks. Patients were routinely contacted regarding their clinical status and treatment compliance. PT was successful in 27 out of 40 patients (68%). Overall AHI reduced significantly from a median (interquartile range [IQR]) AHI of 14.5 (10.7-19.6) to 5.9 (3.1-8.5), p < 0.001. The commercial waistband and self-made constructions were equally effective (median (IQR) reduction in overall AHI (Δ9.6 (5.5-11.9) and Δ6.8 (3.2-11.3) respectively), p = 0.22). Short-term compliance was good as most patients used PT more than 7 hours/night (mean 7.2 ± SD 1.4) and more than 6 days/ week (mean 6.5 ± SD 1.3). However, after mean 13±5 months, 26 patients (65%) reported they no longer used PT, especially patients with moderate positional OSA (89%). On the short-term, PT using the tennis ball technique, is an easy method to treat most patients with positional OSA, showing significant reductions in AHI. Unfortunately, long-term compliance is low and close follow-up of patients on PT with regard to their compliance is necessary.


Incidentally detected prostate cancer in cystoprostatectomy specimens.
Bladder and prostate cancers occur with increasing prevalence in the ageing population. Our study aims to quantify the incidence of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer and assess the impact of that incidental prostate cancer on oncological outcome. We retrospectively reviewed the pathology reports of 128 men who underwent cystoprostatectomy for bladder cancer. Twenty-three men (18%) were found to have incidental prostate cancer. All incidental prostate cancers were organ confined and 91% were well or moderately differentiated. At a mean follow-up of 55 months the prostate cancer-free survival was 96%. The incidence of prostate cancer in cystoprostatectomy specimens is high. When the prostate is removed completely the presence of incidental prostate cancer does not influence the overall oncological outcome.


Lymphokine regulation of macrophage effector activities.
Our concept of the regulation of macrophage activation is ever expanding and contracting. In regard to the number of LK that regulate macrophages killing activities, we have entered a new phase. In the beginning there was one macrophage activation factor, MIF; then there were many macrophage activation factors, most uncharacterized and bearing a variety of names. Then came IFN, a genetically cloned single reagent that induced destruction of virtually every target assessed; all activities of macrophages were assumed to be regulated by IFN. Once again, however, the LK universe is expanding: the number of single, cloned reagents that induce macrophage killing activities is amazing. With just two targets, a fibrosarcoma cell and an intracellular amastigote of L. major, we can identify 5 different macrophage activation factors, four of which are cloned and sequenced. As more recombinant reagents become available, the story of macrophage activation is likely to become even more complex. It is fascinating not only that certain of the LK are capable of inducing single effector reactions in the absence of effects on other effector activities, but also that at least one effector reaction requires the cooperation of several molecularly distinct LK. The complexity of LK activation factors that regulate a single effector reaction in vitro is compounded by the complexity in effector cell populations. For example, inflammatory macrophages exposed to LK kill the fibrosarcoma tumor target 5 to 10-fold better than an equal number of resident peritoneal macrophages. In contrast, LK treated resident macrophages eliminate intracellular amastigotes of leishmania far more efficiently than inflammatory cells. Thus, changes in cell populations dramatically affect the capacity to demonstrate a single effector reaction. Further, simple changes in assay conditions also determine whether an effector reaction can be observed in vitro. And superimposed upon all these layers of complexity is the target itself. The mechanisms a macrophages uses to block the replication of a virus may be totally ineffective in the destruction of a multicellular helminth, such as Schistosoma mansoni. And there is no reason to suspect that the extracellular destruction of a tumor target occurs by the same means that the macrophage uses to kill an intracytoplasmic bacterium, such as a rickettsia.(ABSTRACT TRUNCATED AT 400 WORDS)


Differential effects of reconstituted high-density lipoprotein on coagulation, fibrinolysis and platelet activation during human endotoxemia.
High-density lipoproteins (HDL) can bind and neutralize lipopolysaccharides (LPS) in vitro and in vivo. HDL can also affect fibrinolytic activity and can directly influence platelet function by reducing platelet aggregation. In this study, the effects of reconstituted HDL (rHDL) on LPS-induced coagulation, fibrinolysis and platelet activation in humans were investigated. In a double-blind, randomized, placebo-controlled, cross-over study, eight healthy male volunteers were injected with LPS (4 ng/kg) on two occasions, once in conjunction with rHDL (40 mg/kg, given as a 4 h infusion starting 3.5 h prior to LPS injection), and once in conjunction with placebo. rHDL significantly reduced LPS-induced activation of coagulation (plasma levels of prothrombin fragment F1 + 2) and fibrinolysis (plasma levels of tissue type plasminogen activator antigen, t-PA). No effect was observed on LPS-induced inhibition of the fibrinolytic pathway (PAI-1) or on the transient thrombocytopenia elicited by LPS. Furthermore, rHDL treatment significantly enhanced the inhibition of collagen-stimulated inhibition of platelet aggregation during endotoxemia, but had no such effect on arachidonate-stimulated platelet aggregation. rHDL treatment per se also reduced collagen-induced platelet aggregation. These results indicate that rHDL modifies the procoagulant state associated with endotoxemia.


Agriculture, health, and wealth convergence: bridging traditional food systems and modern agribusiness solutions.
The causes of many vexing challenges facing 21st-century society are at the nexus of systems involved in agriculture, health and wealth production, consumption, and distribution. Using food as a test bed, and on the basis of emerging roadmaps that set achievable objectives over a 1- to 3-year horizon, we introduce this special feature with convergence thinking and practice at its core. Specifically, we discuss academic papers structured around four themes: (1) evidence for a need for convergence and underlying mechanisms at the individual and societal levels; (2) strategy for mainstreaming convergence as a driver of business engagement and innovation; (3) convergence in policy and governance; (4) convergence in metrics and methods. Academic papers under each theme are accompanied by a roadmap paper reporting on the current status of concrete transformative convergence-building projects associated with that theme. We believe that the insights provided by these papers have the potential to enable all actors throughout society to singly and collectively work to build supply and demand for nutritious food, in both traditional and modern food systems, while placing the burdens of malnutrition and ill health on their core strategic agendas.


Association between chronic lymphocytic leukemia and sarcoidosis: clinical value of bronchoalveolar lavage.
We report a case of sarcoidosis, occurred in a patient with chronic lymphocytic leukemia (CLL) shortly following the completion of initial chemotherapy, who relapsed shortly after a second course. Since bronchoalveolar lavage (BAL) demonstrated a predominance of CD4+ lymphocytes, it largely excluded spread of the malignant disorder to the lung, and strongly suggested that sarcoidosis was the cause of the pulmonary infiltrates. This diagnosis was confirmed by the finding of non-caseating granuloma on transbronchial lung biopsy.


Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer.
The expression and function of caldesmon (CAD) in urothelial bladder carcinoma (BC) have not been reported. Here, we investigated the expression, prognostic value, and potential functional mechanism of CAD in primary non-muscle-invasive bladder cancer (NMIBC). Protein profiling of tissue samples using antibody microarrays showed significantly higher CAD expression in muscle-invasive BC tissues compared with NMIBC tissues. We then validated the CAD expression in BC cells by immunohistochemistry analysis using paraffin-embedded tissue blocks and western blots using BC cell lines. In addition, we examined the expression of CAD variants by reverse transcription-polymerase chain reaction, and confirmed the expression of low-molecular-weight isoforms (L-CAD), specifically encoded by WI-38 L-CAD II (transcript variant 2), in BC cells. Survival analysis in an independent primary NMIBC cohort comprising 132 patients showed that positive CAD expression was significantly associated with poorer prognosis than no CAD expression with regard to recurrence- and progression-free survival (p = 0.001 and 0.014, respectively). Multivariate analyses further indicated that positive CAD expression was an independent predictor of progression-free survival (p = 0.032; HR = 5.983). Data obtained from in vitro silencing and overexpression studies indicated that L-CAD promotes migration and invasiveness of BC cells. Immunofluorescence assays showed dramatic structural changes in the actin cytoskeleton of BC cells after L-CAD overexpression. Our findings collectively suggest that L-CAD overexpression in primary NMIBC is significantly associated with tumor progression and that a possible mechanism for L-CAD's activity is implicated in increased cell motility and invasive characteristics through morphological changes in BC cells.


Sildenafil (Viagra) induces powerful cardioprotective effect via opening of mitochondrial K(ATP) channels in rabbits.
Sildenafil citrate (Viagra) is the pharmacological agent used to treat erectile dysfunction in men. Because this drug has a vasodilatory effect, we hypothesized that such an action may induce a preconditioning-like cardioprotective effect via opening of mitochondrial ATP-sensitive K (K(ATP)) channels. Rabbits were treated with sildenafil citrate (0.7 mg/kg iv) either 30 min (acute phase) or 24 h (delayed phase) before 30 min of ischemia and 3 h of reperfusion. Mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg iv) was given 10 min before ischemia-reperfusion. Infarct size was measured by tetrazolium staining. Sildenafil caused reduction in arterial blood pressure within 2 min of treatment, which returned to nearly baseline levels 3 min later. The infarct size (% risk area, means +/- SE) reduced from 33.8 +/- 1.7 in control rabbits to 10.8 +/- 0.9 during the acute phase (68% reduction, P < 0.05) and 19.9 +/- 2.0 during the delayed phase (41% reduction, P < 0.05). 5-HD abolished protection with an increase in infarct size to 35.6 +/- 0.4% and 36.8 +/- 1.6% during the acute and delayed phase, respectively (P < 0.05). Similar acute and delayed cardioprotective effects were observed when sildenafil was administered orally. Systemic hemodynamics also decreased after oral administration of the drug. However, these changes were mild and occurred slowly. For the first time, we demonstrate that sildenafil induces acute and delayed protective effects against ischemia-reperfusion injury, which are mediated by opening of mitochondrial K(ATP) channels.


Molecular evolution and balancing selection in the flavin-containing monooxygenase 3 gene (FMO3).
Flavin-containing monooxygenase 3 (FMO3) is involved in the metabolism of foreign chemicals, including therapeutic drugs, and thus mediates interactions between humans and their chemical environment. Loss-of-function mutations in the gene cause the inherited disorder trimethylaminuria, or fish-odour syndrome. The objective was to gain insights into the evolutionary history of FMO3. Genetic diversity within FMO3 was characterized by sequencing 6.3 kb of genomic DNA, encompassing the entire coding sequence, some intronic and 3'-untranslated region, and 3.4 kb of 5'-flanking sequence, in 23 potential trimethylaminuric Japanese, and the same 3.4 kb 5'-flanking region in 45 unaffected Japanese. Mutational relationships among haplotypes were inferred from a reduced-median network. The time depth of the variation and ages of individual mutations were estimated by maximum-likelihood coalescent analysis. Test statistics were used to investigate whether the variation is compatible with neutral evolution. Sixteen single-nucleotide polymorphisms (SNPs) were identified, which segregated as seven distinct haplotypes. Estimated ages of the mutations indicate that almost all predated migration out of Africa. Analysis of the heterozygosity of FMO3 SNPs indicates that genetic differentiation among continental populations is low (FST=0.050). Test statistics, based on allele-frequency spectrum, number and diversity of haplotypes, linkage disequilibrium and interspecific sequence comparisons, showed a significant departure from neutral expectations, because of an excess of intermediate-frequency SNPs and haplotypes, a ragged pairwise mismatch distribution and an excess of replacement polymorphisms. The results provide evidence that FMO3 has been the subject of balancing selection. Finally, we identify mutations that are potential targets for selection.